A unique type of natural coumarin skeleton-based thiazolylbenzonitriles as novel structural scaffolds to exert potential multitargeting supramolecular antibacterial behavior was developed for the first time from resorcinol through multi-step reactions. All the new compounds were characterized by NMR and HRMS spectra. Structure-activity relationships revealed that the ethoxycarbonyl group was the optimal substituent to exert the effective supramolecular antibacterial action of benzopyronyl thiazolylbenzonitriles (BTBs), and BTB 13a gave an extremely low MIC value of 0.002 mM against Staphylococcus aureus 29213, being 3-fold more active than norfloxacin. Compound 13a exerting the most effective supramolecular antibacterial behaviour possessed favourable druggability with no obvious haemolysis, acceptable cytotoxicity and low propensity to induce bacterial resistance. A series of medicinal chemobiological evaluations disclosed that BTB 13a could not only intercalate into DNA to produce stable biosupramolecular complexes to block DNA replication, and form biosupermolecules with DNA gyrase, but also disturb cell membrane to tempt leakage of intracellular contents, fluctuate the metabolism and induce oxidative stress, finally resulting in bacterial cell death. Moreover, the promising BTB 13a exhibited good in vivo antibacterial efficacy against Staphylococcus aureus 29213. These results implied that benzopyronyl thiazolylbenzonitriles possessed large promise as novel structural antibacterial members to combat Staphylococcus aureus 29213.

Proton transport (PT) in solid-state materials is crucial for applications in energy conversion and protonic devices. Nevertheless, the highly complex and disordered structures of conventional proton-conducting materials, such as polymers and proteins, hinder a clear understanding of the mechanisms underlying PT, particularly the formation of hydrogen bond (H-bond) networks and their role in mediating PT. Here, we show that self-assembling monolayers (SAMs) of oligopeptides provide a promising platform for elucidating the key factors that modulate PT related H-bonds, including amide bond interactions, peptide sequence, and chain length. Combined with structural characterizations of SAMs, the electrical measurements under both direct and alternating current modes demonstrate that longer and more extended oligopeptide chains in SAMs result in an ordered molecular arrangement, leading to a more pronounced response of current density (J) to increasing relative humidity (RH). Moreover, this increase in molecular order also shifts the transition from electron-dominated to proton-dominated charge transport to a higher RH. The synergy between carrier concentration and mobility is a key factor contributing to the increase in J. This study not only elucidates the critical role of ordered H-bonds in PT but also expands the application of SAM technology in controlling molecular conformation and enhancing proton conduction.

Chiral bisoxazoline (box) ligands with indene groups at C4 and C5 are highly potent in asymmetric catalysis, but face challenges in terms of cost and recyclability. To address this, we have designed polystyrene-supported box ligands by modifying the indene moiety instead of the traditional methylene bridge. This design preserves the necessary steric environment for copper coordination, enabling high efficiency and excellent enantioselectivity as examined in photoinduced asymmetric cyanation reactions. The resulting copper complexes are robust and recyclable, maintaining performance over five cycles. This approach provides a sustainable and practical solution for asymmetric catalysis with chiral box ligands.

Reactive oxygen species (ROS) are involved in the onset and development of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Hydrogen peroxide (H₂O₂), a key type of ROS, is overexpressed in the early stages of AD and PD and is involved in the disease progression. Assessing H₂O₂ levels in the brain is considered to be a valuable tool for detecting neurodegenerative diseases and exploring their pathogenesis. In this study, we developed two self-immobilizing PET tracers ([¹⁸F]HYAS and [¹⁸F]HYAT) based on a quinone methide (QM) scaffold for non-invasive imaging of H₂O₂ in the brain. Both tracers can respond to H₂O₂ by forming a QM intermediate, which rapidly reacts with nucleophiles. [¹⁸F]HYAT, with proper physicochemical properties, is able of crossing the blood-brain barrier. Increased uptake of [¹⁸F]HYAT was observed in the brains of mice treated with 1-methyl-4-phenyl- l,2,3,6-tetrahydropyridine (MPTP), indicating that [¹⁸F]HYAT is a useful tracer for PET imaging of H₂O₂ in the brain.

Chain elongation via dinucleotide (dimer) block coupling was considered as an improved chemical technique capable of synthesizing high-quality longer oligonucleotide for de novo DNA synthesis in synthetic biology. However, this dimer block-wise approach was constrained by readily available dimer phosphoramidite with sufficient quality. Herein, through the usage of a one-pot coupling-oxidation-deprotection cascade process for preparing the key precursors 3'-hydroxyl dimers, then condensation with phosphorodiamidite, purification by flash column chromatography and precipation in methyl tert-butyl ether, a rationally designed dimer phosphoramidite bearing an internucleotide allyl phosphate and a β-cyanoethyl phosphoramidite at the 3’-hydroxyl was synthesized. All sixteen allylic dimer phosphoramidites 2a–p were smoothly prepared with overall yields exceeding 50% and HPLC purities ranging from 97.40% to 99.69%. With these allylic reagents, oligonucleotides were successfully synthesized using a modified solid-phase phosphoramidite method and were completely deprotected under normal ammonialysis condition. Our results indicated that these dimer block-wise synthesized oligonucleotides were of sufficient quality for gene assembly and protein expression, thus, the allylic phosphate linked dimer phosphoramidite can serve as a promising dimer reagent that will enable the applications of long oligonucleotides.

Stimuli responsive phosphors with photoluminescence and thermoresponsive luminescence are intriguing for information encryption applications. Herein, two solvent-mediated, stimuli responsive phosphors based on phosphine-copper(I) iodide complexes 1 and 2 are reported. Complex 1 exhibited temperature- and excitation-wavelength-dependent dual-emission characteristics, displaying high energy (HE) and low energy (LE) bands with the quantum yield (QY) of 38.5% under 365 nm irradiation; but complex 2 exhibited no emission. The LE emission can be attributed to a triplet halide-to-metal charge transfer (³XMCT) and copper-centered 4d→3s, 3p transitions, whereas the HE emission originates from a triplet halide-to-ligand charge-transfer (³XLCT). Importantly, in complex 2, the strong C—H∙∙∙Cl interaction in the supramolecular crystal lattice annihilated the sensitive cluster centered (³CC) excited state. Intriguingly, only the HE emission band of complex 2 can be successfully activated by high-energy excitation or changing the temperature. Nevertheless, the QY of complex 2 is 15.6% under 310 nm irradiation, which is smaller than that of complex 1 of 49.8%. This behavior was further confirmed by heating, where both complexes show HE emission. The reversible crystal transformation between complexes 1 and 2 was achieved. Furthermore, the reversible excitation-wavelength-dependent dual-emission and thermoresponsive properties make these phosphors suitable candidates for anti-counterfeiting and information encryption applications.

Visible-light-driven photocatalysis has great potential in environmental remediation and organic synthesis. Rational design and regulation of the reaction interfacial microenvironment is critical for photocatalytic performance, yet challenging. We report here a highly efficient photocatalytic system based on hydrophobic TiO₂ porous (H-OTP) film for visible-light-driven dye-sensitized photo-oxidation. Such interface architecture design enhances the adsorption capability of organic dyes and enables the formation of air trapped triphase reaction interface microenvironment as confirmed via three-dimensional (3D) laser scanning confocal microscopy. Based on this interface architecture, the concentrations of O₂ and organic molecule at the local reaction zone are both significantly increased, which promotes the generation of reactive oxygen species (•O₂⁻ and •OH), and enhances the photocatalytic performance in terms of both kinetics and organic mineralization efficiency. This study highlights the importance of interface microenvironment design and reveals an effective way to develop highly efficient photocatalytic systems.

The development of new strategy for environmentally friendly, cost-effective and large-scale electro-synthesis of anticancer drugs is highly desirable to replace high-cost traditional methods and realize high atomic economy. GW 610, an antitumor agent with potent and selective anticancer activity against lung, colon, and breast cancer cell lines in real medical treatment processes, has a market price of ~10⁷ USD/kg and calls for novel methods like electro-synthesis to reduce the cost. Here, for the first time, we design a solid-liquid-gas three-phase indirect electrolysis system based on a kind of microwave-synthesized polyoxometalate-based metal-organic framework (MW-POMOF) that can converse S–S bond substrates into valuable C–S bond products like anticancer drug molecules (e.g., GW 610). Specifically, the solid-phase MW-POMOF as heterogeneous redox mediator exhibits the excellent electrocatalytic efficiency for the formation of liquid-phase C–S bond products (yields up to 95%) coupling with the generation of gas-phase H₂ product (~402 μmol·g^–1·h^–1), resulting in an interesting three-phase indirect electrolysis system. Remarkably, it enables the kilo-scale production (~1 kg in a batch experiment) of GW 610 at one thousandth of the market price (from ~10⁷ to ~3200 USD/kg). This work may inaugurate a new electrocatalytic avenue to explore porous crystalline materials in electrocatalysis field.

An efficient photoredox/copper dual-catalyzed 1,2-diphosphorothiolation of alkenes with P(O)SH compounds was realized under oxidative conditions. In this transformation, P(O)SH acted as both the phosphorothioate radical source and the coupling partner. A wide range of valuable vicinal bisphosphorothioates can be easily constructed starting from simple raw materials in a step- and atom-economical manner. Notably, this reaction system has been successfully used to incorporate two phosphorothioate groups into many drug molecules, highlighting the substantial synthetic potential of this protocol.

We report an N-heterocyclic carbene (NHC)-catalyzed [10π+2π] cycloaddition between indene-2-carbaldehydes and isatins, delivering spirooxindole-γ-butyrolactones with moderate yields (up to 68%) and excellent enantioselectivity (up to 93% ee). This transformation proceeds via NHC-bound isobenzofulvene intermediates and represents the first successful application of all-carbon higherene in NHC-catalyzed [10π+2π] cycloadditions.

A dual catalytic manifold that combines photoredox catalysis and phthalate-catalyzed hydrogen-atom abstraction process has been developed to realize diverse fragmentation-functionalization reactions. Key to success is photocatalytic generation of tether-tunable distonic radical anions (TDRAs) as proton-coupled electron transfer mediators, enabling polarity-matching-based formation of heteroatom-centered radicals that allows for further controlled exploration of chemical space via C–C β-scission. These reactions feature exceptionally broad substrate generality, gram-scale synthesis, potential biocompatibility and late-stage modification of complex molecules, while obviating the use of stoichiometric and often unsafe peroxides in our previous studies. Mechanistic studies support a redox-neutral radical relay pathway enabled by in situ-generated, catalytic TDRAs.

Visible light-induced transformation of CO₂ and CS₂ into value-added products has attracted worldwide attention because it mimics nature. In this context, although visible-light-induced direct synthesis of dithiocarbamates and carbamates employing SO₂ and CO₂ as a C1 source has been reported, all these reactions are limited to the preparation of S-alkyl mono-dithiocarbamates and O-alkyl mono-carbamates. Herein, we report a visible-light photoredox-catalyzed multicomponent reaction of diazosulfonium triflates with amines and CS₂ or CO₂. Mechanistic studies indicate that the diazomethyl radicals might be generated as the key intermediates, thus providing a direction for the application of diazomethyl radicals with other radical acceptors.

This study presents an efficient and innovative allylation strategy utilizing C/N/O nucleophilic reagents with attenuated reactivity, enabling the construction of versatile allyl compounds. The approach focuses on the sequential allylation of dihalides in large-scale chemical manufacturing, effectively addressing the challenge of achieving selectivity in cascade reactions. The methodology is centered on the Cu-catalyzed C-olefination of alkynes with dihalides, significantly expediting the synthesis of a diverse array of finely conjugated enyne derivatives. Furthermore, a base-facilitated sequential condensation process has been developed to achieve the N-allylation of hydrazines, yielding a wide range of trisubstituted alkenyl hydrazones. Additionally, the protocol enables the synthesis of high-value ester compounds through O-allylation or esterification with dihalides. This transformation also facilitates the one-step synthesis of a variety of essential pharmaceuticals, demonstrating its broad synthetic utility and potential.

Herein, we present a highly efficient one-pot, two-step synthesis of β-hydroxy nitrile scaffolds, which possess both significant synthetic value and notable biological activity, starting from readily accessible alkenes. This methodology relies crucially on the seamless integration of a highly regioselective (3+2) cycloaddition reaction, employing the commercially available 1,1-dibromoformaldoxime as the 1,3-dipole precursor, with a subsequent halogen atom transfer-induced radical ring-opening elaboration of the resulting 3-bromo-2-isoxazoline cycloadducts. This protocol is featured by mild reaction conditions, broad alkene scope and various derivatizations of the obtained cyano-hydroxylation products, offering a versatile and practical pathway to accessing multi-functionalized molecules.

Supramolecular organogels were highly promising matrices for triplet–triplet annihilation-based upconversion (TTA-UC), but the dispersion and diffusion of the UC components were greatly relied on the microscopically interconnected solution phase in gels. Herein, 12-hydroxystearic acid (CA) and its derivatives with different alkyl chain (CA3, CA4, CA6 and CA8) were synthesized as low-molecular-weight gelators (LMMGs), and D-1 with CA attached on DPA unit was synthesized as annihilator. It was found that by co-assembling D-1 with the LMMGs, the DPA units were uniformly dispersed in the gel network regardless of whether there was a solvent or not. By chemically tuning LMMGs to optimize the morphologies of organogels, the DPA units were orderly arranged in the gel network, and showing efficient UC emission in CA, CA3, and CA8 which showed more regular morphologies. UC quantum yield of up to 13.4% (out of 50% maximum) was achieved in CA3 organogel. Moreover, when all solvents were removed from the organogels, D-1 also showed significant UC emissions, which was more than 6-fold higher than that of DPA, indicating that co-assembling the annihilator with the matrix to achieve an order arrangement presented an efficient strategy towards efficient TTA-UC in solid state.

The asymmetric cycloaddition reactions of 1,3-fused cyclic azomethine ylides have been extensively studied, but the non-cyclic α-functionalization of these compounds remains unexplored. Herein, an efficient combination of the catalytic enantioselective non-cyclic α-functionalization of 1,3-fused cyclic azomethine ylides and the remote-controlled asymmetric desymmetrization of N-arylmaleimides and cyclopentene-1,3-diones has been achieved with a catalyst system consisting of a chiral P,N-ferrocene ligand and AgNO₂. This reaction allowed for the synthesis of a series of enantioenriched 3,4-dihydroisoquinoline derivatives bearing multiple stereogenic elements/centers with good yields and stereoselectivities. The practicality of this method was demonstrated by gram-scale synthesis and derivatizations of the products.

Microfluidic technology is an emerging arena that manipulates tiny fluids through the use of microchannels, which typically range in dimensions from tens to hundreds of micrometers. This technology has been widely applied in chemical analysis, biological detection, and materials synthesis due to its precise processing and manipulation of tiny fluids. Moreover, droplet microfluidics with polydimethylsiloxane (PDMS) devices is one of the most famous ways to carry out some applications or investigations that were not previously possible using conventional techniques. This review covers the mechanisms of droplet formation, innovative applications in synthesis, and potential integration with advanced techniques. Precise control over microfluidic channels, excellent efficiency, product consistency, and high-throughput screening capabilities are highlighted. In this respect, employing this technology in the synthesis of nanomaterials, small molecules, and polymers is discussed, as well as facilitating the development of novel materials. Additionally, we discuss future prospects, including optimizing device design, integrating with cutting-edge technologies, and advancing precision medicine. Despite challenges related to device complexity and fabrication costs, the potential for resolution through new materials and methods underscores the critical role of droplet microfluidics in scientific innovation.

Self-assembly processes are ubiquitous in biological systems, playing essential roles in sustaining life activities. The exploration of self-assembled biomaterials (SABMs) holds great potential for advancing various fields, particularly in biomedicine and materials science. Because of the unique reversibility and responsiveness to stimuli, dynamic covalent bonds (DCBs) and noncovalent bonds (NCBs) endow SABMs with self-healing properties, stimuli responsiveness and controllable degradation, making them highly versatile for a wide range of biomedical applications. In this article, recent advances and future trends for SABMs based on DCBs and NCBs are thoroughly reviewed. We begin by introducing the molecular principles and characteristics of DCBs and NCBs that govern the formation of SABMs. We also explore the responsive and functional features of these materials in detail. Finally, we summarize the perspectives and challenges associated with the development of SABMs in biomedical applications. We aim for this review to offer a comprehensive overview of SABMs, serving as a valuable resource for chemists and materials scientists striving to further advance the design of SABMs in biological applications.

DNA synthesis and assembly technology is the fundamental enabling technology of synthetic biology, providing methods for humans to understand and modify organisms. Oligonucleotide chains and long DNA fragments synthesized through DNA synthesis and assembly technology are becoming increasingly widely used in fields such as biomedicine, energy, new materials, and information storage, with strong application prospects. This review provides a comprehensive and systematic introduction and exposition of current DNA synthesis and assembly technologies, discussing current challenges and future research prospects.